The study found that rapamycin may decrease chondrocyte proliferation, alter the maturation of hypertrophic chondrocytes, delay vascular invasion, and reduce tartrate resistant acid phosphatase (TRAP) activity in the chondro-osseous junction in the growth plate cartilage.
The study suggests that the effects of rapamycin on the growth plate need further evaluation, especially in young children who are on long-term immunosuppressant therapy with rapamycin. The dose of rapamycin used in the study was higher than the currently prescribed dose for pediatric patients, but similar doses have been used in previous animal studies.
The findings indicate that the growth plate cartilage showed enlargement of the hypertrophic zone, possibly due to a decrease in proliferating chondrocytes and reduced cartilage resorption. However, body length and tibial length measurements remained short, suggesting that catch-up growth may be needed for the rapamycin-treated animals.
Rapamycin is known for its immunosuppressive effects, and it inhibits cell cycle progression and DNA synthesis. In this study, chondrocyte proliferation was significantly decreased, along with a decrease in markers of chondrocyte proliferation such as histone 4 and mTOR expression. Additionally, there was a downregulation of type II collagen expression, which is important for the support of chondrocytes in the extracellular matrix.
The study also observed changes in the expression of parathyroid hormone-related protein (PTHrP) and Indian hedgehog (Ihh) after two weeks of rapamycin treatment. However, these changes were not significant after four weeks.
In conclusion, this study suggests that rapamycin can affect the growth plate cartilage in young rats by altering chondrocyte proliferation, maturation, vascular invasion, and TRAP activity. Further research is needed to understand the implications of these findings, especially in young children on long-term rapamycin therapy.
